Microorganisms, such as bacteria, mycobacteria or fungi, may colonize surfaces, forming a structure called “biofilm” as a defense against antimicrobial agents and other environmental hazards. A biofilm is a layer comprising an aggregate of microorganisms, wherein each cell adheres to each other. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance (EPS)—a polymeric conglomeration generally composed of extracellular DNA, proteins, and polysaccharides. Biofilms may form on living or non-living surfaces and can be prevalent in natural, industrial and hospital settings (Hall-Stoodley et al., 2004, Nature Rev. Microbiol. 2(2):95-108; Lear & Lewis, eds., 2012, “Microbial Biofilms: Current Research and Applications”, Caister Academic Press, 2012). The microbial cells growing in a biofilm are physiologically distinct from single planktonic cells of the same organism, which float or swim in a liquid medium.
Microbes form a biofilm in response to factors such as cellular recognition of specific or non-specific attachment sites on a surface; nutritional cues; or exposure to sub-inhibitory concentrations of antibiotics (Karatan & Watnick, 2009, Microbiol. Mol. Biol. Rev. 73(2):31047; Hoffman et al., 2005, Nature 436(7054):1171-5). When a cell switches to the biofilm mode of growth, it undergoes a phenotypic shift in behavior in which large suites of genes are differentially regulated (An & Parsek, 2007, Curr. Op. Microbiol. 10(3):292-6).
Biofilms are involved in as much as 80% of all microbial infections (“Research on microbial biofilms (PA-03-047),” NIH, National Heart, Lung, and Blood Institute, December 2012). Infectious processes in which biofilms have been implicated include common problems (such as urinary tract infections, catheter infections, middle-ear infections, formation of dental plaque, gingivitis, and coating of contact lenses), and less common but more lethal processes (such as endocarditis, infections in cystic fibrosis, and infections of permanent indwelling devices such as joint prostheses and heart valves) (Rogers, 2008, “Molecular Oral Microbiology,” Caister Academic Press, pp. 65-108; Imamura et al., 2008, Antimicrob. Agents Chemother. 52(1):171-82; Lewis, 2001, Antimicrob. Agents Chemother. 45(4):999-100; Parsek & Singh, 2003, Ann. Rev. Microbiol. 57:677-701). In fact, bacterial biofilms may impair cutaneous wound healing and reduce topical antibacterial efficiency in healing or treating infected skin wounds (Davis et al., 2008, Wound Rep. Regen. 16(1):23-9).
Biofilms can also be formed on the inert surfaces of implanted devices such as catheters, prosthetic cardiac valves and intrauterine devices (Auler et al., 2009, Med. Mycol. 1-6). Antimicrobial agents (such as antibiotics or antiseptics) are generally not much active in killing or inhibiting the microorganisms that are deeply embedded within the biofilm, in part due to the shielding effect of the biofilm.
There is a need in the art for novel antimicrobial or biofilm-penetrating compositions. These compositions may be used to remove at least a portion of or reduce the number of the microorganisms or biofilm-embedded microorganisms attached to the surface of a medical device or the surface of a subject's body. These compositions may also be used to coat medical devices, thus inhibiting microbial growth or disrupting the biofilm and allowing antimicrobial agents and/or antifungal agents to penetrate the biofilm and kill the microorganisms located therein. These compositions may also be used to prevent or reduce the growth or proliferation of microorganisms or biofilm-embedded microorganisms on the surface of a medical device or on the surface of a subject's body. The present invention fulfills these needs.